Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PKN, a novel protein kinase with a catalytic domain homologous to that of the protein kinase C (PKC) family and unique N-terminal leucine-zipper-like sequences, was identified by molecular cloning from a human hippocampus cDNA library [Mukai and Ono (1994) Biochem. Biophys. Res. Commun. 199, 897-904]. Recently we partially purified recombinant PKN from COS7 cells transfected with the cDNA construct encoding human PKN, and demonstrated that the recombinant PKN was activated by unsaturated fatty acids and limited proteolysis [Mukai, Kitagawa, Shibata et al. (1994) Biochem. Biophys. Res. Commun. 204, 348-356]. The present work has focused on the further purification and characterization of PKN from native rat tissue. Immunochemical measurement revealed that PKN was found in every tissue, and was especially abundant in testis, spleen and brain; subcellular fractionation of rat brain showed that half of the PKN was localized in the soluble cytosolic fraction. PKN was purified approx. 8000-fold to apparent homogeneity from the cytosolic fraction of rat testis by DEAE-cellulose chromatography, ammonium sulphate fractionation and chromatography on butyl-Sepharose, heparin-Sepharose, Mono Q and protamine-CH-Sepharose. The enzyme migrates as a band of apparent molecular mass 120 kDa. Using serine-containing peptides based on the pseudosubstrate sequence of PKC-delta as phosphate acceptors, the kinase activity was stimulated several-fold by 40 microM unsaturated fatty acids or by detergents such as 0.04% sodium deoxycholate and 0.004% SDS. In the absence of modifiers, protamine sulphate, myelin basic protein and synthetic peptides based on the pseudosubstrate site of PKCs or ribosomal S6 protein were good substrates for phosphorylation by the kinase. In the presence of 40 microM arachidonic acid the kinase activity of PKN for these phosphate acceptors was increased 2-18-fold. The autophosphorylation activity of purified PKN was partially inhibited by pretreatment with alkaline phosphatase. These properties appear to distinguish PKN from many protein kinases isolated previously.
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PMID:Purification and characterization of a fatty acid-activated protein kinase (PKN) from rat testis. 765 8

PKN, a novel protein kinase with catalytic domain homologous to PKC family and unique amino terminal leucine zipper-like sequences, was purified partially from COS7 cells transfected with the cDNA construct encoding human PKN for enzymatic characterization of the enzyme. Using serine containing synthetic peptides based on PKC pseudosubstrate sites as the phosphate acceptors, kinase activities estimated from partially purified PKN were not stimulated by Ca2+/phosphatidylserine/diolein but were activated several-fold to several tens-fold by 40 microM unsaturated fatty acids, such as arachidonic acid, linoleic acid, and oleic acid. Autophosphorylation of the immunoprecipitates using anti-PKN antiserum was also stimulated by various unsaturated fatty acids. Limited proteolysis of PKN with trypsin induced an enhancement of the peptide kinase activity that was almost independent of arachidonic acid.
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PMID:Activation of PKN, a novel 120-kDa protein kinase with leucine zipper-like sequences, by unsaturated fatty acids and by limited proteolysis. 794 81

A novel protein kinase, designated PKN, was identified by molecular cloning from a human hippocampus cDNA library. PKN consists of 942 amino acids with a calculated molecular mass of 103,925 daltons. PKN has leucine zipper-like sequences in its amino terminal region and contains a catalytic domain that shows strong similarity to that of protein kinase C family. Northern blot analysis indicates PKN is expressed ubiquitously in human tissues. Antisera against PKN identified a 120K dalton protein on SDS polyacrylamide gel electrophoresis when PKN was expressed in the insect cells or COS7 cells. Recombinant PKN revealed an intrinsic protein kinase activity associated with a 120K protein. This activity was abolished by mutation of the lysine residue in the potential ATP binding site.
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PMID:A novel protein kinase with leucine zipper-like sequences: its catalytic domain is highly homologous to that of protein kinase C. 813 37

The Rho guanosine 5'-triphosphatase (GTPase) cycles between the active guanosine triphosphate (GTP)-bound form and the inactive guanosine diphosphate-bound form and regulates cell adhesion and cytokinesis, but how it exerts these actions is unknown. The yeast two-hybrid system was used to clone a complementary DNA for a protein (designated Rhophilin) that specifically bound to GTP-Rho. The Rho-binding domain of this protein has 40 percent identity with a putative regulatory domain of a protein kinase, PKN. PKN itself bound to GTP-Rho and was activated by this binding both in vitro and in vivo. This study indicates that a serine-threonine protein kinase is a Rho effector and presents an amino acid sequence motif for binding to GTP-Rho that may be shared by a family of Rho target proteins.
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PMID:Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho. 857 Nov 26

PKN is a newly discovered protein kinase that has been shown to mediate GTPase Rho dependent intracellular signalling. We show in this report that the mouse PKN gene is situated at the mouse EP1 prostanoid receptor gene locus and that the two genes are overlapping in a tail-to-tail manner. An "exon trap" strategy was used to identify the overlap phenomenon. By using RT-PCR and 3' RACE we have identified two major PKN transcripts that are produced by alternative polyadenylation. The 3' end of the short PKN transcript overlaps the 3' untranslated region of the EP1 gene with approximately 280 bp, while the long PKN transcript overlaps the whole EP1 gene. Remarkably, none of the three transcripts originating from this locus display the consensus AAUAAA polyadenylation signal. The last seven exons of the PKN gene, corresponding to the last third of the PKN cDNA, have been recognised in 7.2 kb of continuous genomic sequence that we have collected from the EP1/PKN genetic locus. The 3' part of the PKN gene is highly fragmented and its intron/exon organisation is reminiscent of that of the Drosophila protein kinase C gene. The possibility of a natural antisense regulation of these genes is discussed.
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PMID:The mouse genes for the EP1 prostanoid receptor and the PKN protein kinase overlap. 885 5

The NCK adapter protein is comprised of three consecutive Src homology 3 (SH3) protein-protein interaction domains and a C-terminal SH2 domain. Although the association of NCK with activated receptor protein-tyrosine kinases, via its SH2 domain, implicates NCK as a mediator of growth factor-induced signal transduction, little is known about the pathway(s) downstream of NCK recruitment. To identify potential downstream effectors of NCK we screened a bacterial expression library to isolate proteins that bind its SH3 domains. Two molecules were isolated, the Wiskott-Aldrich syndrome protein (WASP, a putative CDC42 effector) and a serine/threonine protein kinase (PRK2, closely related to the putative Rho effector PKN). Using interspecific backcross analysis the Prk2 gene was mapped to mouse chromosome 3. Unlike WASP, which bound the SH3 domains of several signaling proteins, PRK2 specifically bound to the middle SH3 domain of NCK and (weakly) that of phospholipase Cgamma. PRK2 also specifically bound to Rho in a GTP-dependent manner and cooperated with Rho family proteins to induce transcriptional activation via the serum response factor. These data suggest that PRK2 may coordinately mediate signal transduction from activated receptor protein-tyrosine kinases and Rho and that NCK may function as an adapter to connect receptor-mediated events to Rho protein signaling.
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PMID:Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling. 891 May 19

PKN is a fatty acid- and Rho-activated serine/threonine protein kinase, having a catalytic domain homologous to protein kinase C family. To identify components of the PKN-signaling pathway such as substrates and regulatory proteins of PKN, the yeast two-hybrid strategy was employed. Using the N-terminal region of PKN as a bait, cDNAs encoding actin cross-linking protein alpha-actinin, which lacked the N-terminal actin-binding domain, were isolated from human brain cDNA library. The responsible region for interaction between PKN and alpha-actinin was determined by in vitro binding analysis using the various truncated mutants of these proteins. The N-terminal region of PKN outside the RhoA-binding domain was sufficiently shown to associate with alpha-actinin. PKN bound to the third spectrin-like repeats of both skeletal and non-skeletal muscle type alpha-actinin. PKN also bound to the region containing EF-hand-like motifs of non-skeletal muscle type alpha-actinin in a Ca2+-sensitive manner and bound to that of skeletal muscle type alpha-actinin in a Ca2+-insensitive manner. alpha-Actinin was co-immunoprecipitated with PKN from the lysate of COS7 cells transfected with both expression constructs for PKN and alpha-actinin lacking the actin-binding domain. In vitro translated full-length alpha-actinin containing the actin-binding site hardly bound to PKN, but the addition of phosphatidylinositol 4, 5-bisphosphate, which is implicated in actin reorganization, stimulated the binding activity of the full-length alpha-actinin with PKN. We therefore propose that PKN is linked to the cytoskeletal network via a direct association between PKN and alpha-actinin.
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PMID:Interaction of PKN with alpha-actinin. 903 May 26

PKN is a serine/threonine protein kinase with a catalytic domain homologous to the protein kinase C family and unique N-terminal leucine zipper-like sequences. Using analyses with the yeast two-hybrid system and in vitro binding assay, we found that the regulatory domain of PKN interacted with vimentin. We then examined whether PKN would phosphorylate vimentin in vitro. Vimentin proved to be an excellent substrate for PKN, and the phosphorylation of vimentin by PKN occurred in the head domain with the result of a nearly complete inhibition of its filament formation in vitro. Similar results were also obtained with another type III intermediate filament protein, glial fibrillary acidic protein (GFAP). These results raise the possibility that PKN may regulate filament structures of vimentin and GFAP by domain-specific phosphorylation.
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PMID:Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN. 917 63

Protein kinase B (PKB, also named as Akt or RAC-protein kinase), that is activated by cellular stress such as heat shock and hyperosmotic treatment, was revealed to be activated by oxidative stress and by chemical stressors of CdCl2 and NaAsO2 by measuring the activity of the enzyme immunoprecipitated from the transfected COS-7 cells. Upon stress treatment, a 30-kDa phosphoprotein was co-immunoprecipitated with PKB from the cells metabolic labeled with [32P]orthophosphate. The phosphoprotein was identified as Hsp27, a small heat shock protein, by immunoblot analysis and co-immunoprecipitation. The association of Hsp27 was specific to PKB as the heat shock protein was not co-immunoprecipitated with other protein kinases such as protein kinase C and PKN. When the cells were treated with H2O2, PKB was activated gradually and the association of Hsp27 with PKB increased concurrently with the enhancement of PKB activity. In heat-shocked cells, activation of PKB and the association of Hsp27 were detected immediately after the treatment, and the association of the heat shock protein decreased while PKB kept stimulated activity when the cells were further incubated at 37 degrees C. These results suggest that Hsp27 is involved in the activation process of PKB in the signal transduction pathway of various forms of stress.
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PMID:Activation of protein kinase B (Akt/RAC-protein kinase) by cellular stress and its association with heat shock protein Hsp27. 923 90

PRK1 (PKN) is a serine/threonine kinase that has been shown to be activated by RhoA (Amano, M., Mukai, H., Ono, Y., Chihara, K., Matsui, T., Hamajima, Y., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) Science 271, 648-650). Detailed analysis of the PRK1 region involved in RhoA binding has revealed that two homologous sequences within the HR1 domain (HR1a and HR1b) both bind to RhoA; the third repeat within this domain, HR1cPRK1, does not bind RhoA. The related HR1 motif is also found to confer RhoA binding activity to the only other fully cloned member of this kinase family, PRK2. Furthermore, the predictive value of this motif is established for an HR1a sequence derived from a Caenorhabditis elegans open reading frame encoding a protein kinase of unknown function. Interestingly, the HR1aPRK1 and HR1bPRK1 subdomains are shown to display a distinctive nucleotide dependence for RhoA binding. HRIaPRK1 is entirely GTP-dependent, while HR1bPRK1 binds both GTP- and GDP-bound forms of RhoA. This distinction indicates that there are two sites of contact between RhoA and PRK1, one contact through a region that is conformationally dependent upon the nucleotide-bound state of RhoA and one that is not. Analysis of binding to Rho/Rac chimera provides evidence for a HR1aPRK1 but not HR1bPRK1 interaction in the central third of Rho. Additionally, it is observed that the V14RhoA mutant binds HR1a but does not bind HR1b. This distinct binding behavior corroborates the conclusion that there are independent contacts on RhoA for the HR1aPRK1 and HR1bPRK1 motifs.
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PMID:Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif. 944 75


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